Newly-constructed strains of adenovirs, containing temperature-sensitive, hostrange and endonuclease site markers, are to be used to determined the mechanism of adenovirus recombination. The segregation of these markers in appropriate crosses will indicate whether or not recombination is uniform throughout the genome, is reciprocal, and is affected by regions of DNA heterology. The data will be analyzed to distriminate between a meiotic, reciprocal, model of recombination and two non-reciprocal 'strand uptake' models that differ in the event that initiates recombination. To investigate the role of mis-match repair in adenovirus recombination, DNA-mediated transfection of coplete or partial heteroduplexes will be examined. The segregation of heteroduplex restriction sites, under conditions of DNA replication block, will be determined by hybridization of intracellular DNA with probes capable of detecting specific recombinant DNA molecules. The recombinant molecules will arise only if mis-match repair has taken place. The length of heteroduplex tracts is to be estimated by a set of crosses involving 'overlap recombination' between oppposiote terminal DNA fragments obtained from several hexon ts alleles. Using various metabolic inhibitors, and mutations in several early gene functions, experiments are designed to determine the requirement for early gene products in adenovirus recombination. Analysis will be either by scoring of viral genotypes in productive infections or by hybridiation of intracellular DNA. Some preliminary experiments are described to determine whether or not in vitro DNA replication systems permit recombination.